#2020BSQ-NOV/Q10
#2020BSQ-NOV/Q20
| Carbimazole / methimazole | Propylthiouracil |
|---|---|
| Less severe side effects. Usually first line choice | Usually second line, except T1 of pregnancy, <- preferred in T1 and thyroid storm |
| Blocks 5'-monodeiodinase, which converts peripheral T4 to T3 conversion | |
| Less frequent teratogenic effects | |
| Pruritus, rash, arthritis, urticaria, abnormal taste | Same |
| Agranulocytosis (0.1% incidence) | Same |
| Less risk of hepatic injury (?can cause cholestatis) | Fulminant hepatic failure |
| ANCA positive vasculitis |
#2020BSQ-NOV/Q18
Adverse drug reaction: A noxious and unintended response to a drug that occurs during usual clinical use.
Adverse drug event: any unexpected or inappropirate occurence that occurs during drug administration. Does not necessarily have a causal relationship to the drug administration.
Intentional overdose and prescribing errors are not adverse drug reactions.
What is meant by idiosyncratic:
Drug idiosyncrasy—A genetically determined, qualitatively abnormal reaction to a drug related to a metabolic or enzyme deficiency
(i.e when some patient factor interacts with drug pharmacology to create the adverse reaction).
| Type | Description | Comments | Example |
|---|---|---|---|
| Type A | Augmented - Dose dependent | Can occur at normal or abnormal doses | Serotonin syndrome, bleeding with heparin etc. |
| B | Bizarre - non dose related | Any exposure is enough to tigger the reaction | Anaphylaxis, idiosyncratic reactions |
| C | Chronic - dose and time related | Occurs due to dose accumulation | Adrenal suppresion with corticosteroids |
| D | Delayed - time related | Due prolonged use without dose accumulation | tardive dyskinseia with atypical antipsychotics |
| E | End of use | Adverser events on withdrawa | Opiate withdrawal, rebound hypertension with clonidine |
| F | Failure | Undesirable reduction in drug efficacy | Like drug efficacy reduced by dialysis |
[!TIP] mnemonic: 'flozins' are SGLT-2 inhibitors
Glucose 'flows in' the PCT
| Sitagliptin Linigliptin | DPP-4 inhibitors (gliptins) | Inhibit GLP-1 breakdown (restore physiologic GLP levels) → promotion of insulin secretion GLP1 receptors are also found in the cardiovascular system | Good S/E profile. | Used as second line drug, in early DM when insulin secretion is still preserved. Combined with metformin / sulfonylurea | Modest effect but used because of low S/E profile. |
Basis: GLP-1 and GIP are incretin hormones.
Reduce apetite -> weight loss
No benefit from combining with DPP4 inhibitors.
Effective renal plasma flow can be calculated using the Fick principle with para-amino hippuric acid. This is a substance that is filtered and secreted by the kidney (but not reabsorbed) meaning that almost all of it is removed in a pass through the kidney. (extraction ratio is around 90%).
#2020BSQ-NOV/Q02
It is the most common cause of lactase deficiency, also known as lactase non-persistence. There is a gradual decline in lactase enzyme activity with increasing age. Enzyme activity begins to decline in infancy, and symptoms manifest in adolescence or early adulthood.
Secondary Lactase Deficiency
Due to several infectious, inflammatory, or other diseases, injury to intestinal mucosa can cause secondary lactase deficiency. Common causes include:
There are 4 types of receptors:
[!TIP]
This Source is very good and agrees with Rang and Dale but is much shorter and is the source for all the images.
Incredibly short overview:
| Ligand gated ion channels | GPCR | Receptor Kinases | Nuclear receptors |
|---|---|---|---|
| Muscarinic ACh receptors | |||
| [[adrenoceptors.png|Adrenoceptors]] | |||
| Dopamine receptor | |||
| 5-HT receptor | |||
| Chemoreceptors in the nose | |||
| opioid | |||
| Cannabinoid | |||
| Catecholamines, histamines, serotonine | |||
[!TIP]
The nitocinic receptors (which is a ligand gated ion channel) is found at the neuromusclar junction.
One of the targets of G proteins.
Alveolar arterial oxygen gradient increases in CO poisoning.
Antipseudomonal carbapenems – imipenem, meropenem and doripenem – have excellent activity against most strains of many bacterial species and are regarded as safe and generally well-tolerated. Of note, these carbapenems are resistant to ESBLs, and so are of value in treating infections caused by ESBL-producing strains of Enterobacteriaceae
Source
#2020BSQ-NOV/Q19
[!INFO] Pharmacokinetics Vs. Pharmacodynamics
Dynamics = 'power'
Pharmacodynamics = effect drugs have on the body.
Pharmacokinetics = effect body has on drug concentrations.
#2020BSQ-NOV/Q17
$$
Bioavailability=\frac{AUC_{oral}}{AUC_{IV}}
$$
where AUC = area under the curve for drug concentration Vs. time graph.
[!INFO]
Extraction ratio : Hepatic extraction ratio ... is the fraction of the drug entering the liver in the blood which is irreversibly removed (extracted) during one pass of the blood through the liver.
$$
\large Extraction\space Ratio = \frac{C_{arterial} - C{venous}}{C_{arterial}}
$$
Protein binding affects hepatic extraction ratio because hepatocytes have access only to the unbound form of the drug.
Therefore, the equation above is equivalently represented as
$$
\large E_H = \frac{fu\times Cl_{int}}{Q_{H}+fu\times Cl_{int}}
$$
- (EH = hepatic extraction ratio)
- (Cl = intrinsic clearance)
- Intrinsic clearance is the intrinsic ability of the liver to remove (metabolise) the drug in absence of restrictions imposed on drug delivery to the liver cell by blood flow or protein binding.
- It basically expresses how powerful the liver enzymes are at removing a drug.
- Fu - Fraction of unbound drug in the plasma
- QH - hepatic blood flow
Finally we have the following equation for hepatic clearance: (ClH)
$$
\large Cl_{H} = Q_{H} \times \frac{fu\times Cl_{int}}{Q_{H}+fu\times Cl_{int}}
$$
So, we can see that hepatic clearance is affected by
- Hepatic blood flow
- Unbound fraction of the drug
- Intrinsic ability of the liver to metabolize the drug
[!INFO] The upshot
Drugs with low intrinsic clearance will have "intrinsic limited" clearance
Drugs with high intrinsic clearance will have "flow limited" clearance.
In liver failure,
The A-a gradient tends to increases with age.
(A-a gradient = 2.5 + FiO2 x age in years<-- Source )
Of the 5 causes of hypoxaemia, elevated A-a gradient excludes hypoventilation and low FiO2 as the causes.
The 5 causes must be written down somewhere else but just in case:
Increased in
Normal in